Knockdown of orexin/hypocretin 2 receptor (Orx) in the basolateral amygdala (BLA) affects anxious and depressive behavior. We use a new behavioral paradigm, the Stress Alternatives Model (SAM), designed to improve translational impact. The SAM induces social stress in adult male mice by aggression from larger mice, allowing for adaptive decision-making regarding escape. In this model, mice remain (Stay) in the oval SAM arena or escape from social aggression (Escape) via routes only large enough for the smaller mouse. We hypothesized intracerebroventricular (icv) stimulation of Orx receptors would be anxiolytic and antidepressive in SAM-related social behavior and the Social Interaction/Preference (SIP) test. Conversely, we predicted that icv antagonism of Orx receptors would promote anxious and depressive behavior in these same tests. Anxious behaviors such as freezing (both cued and conflict) and startle are exhibited more often in Stay compared with Escape phenotype mice. Time spent attentive to the escape route is more frequent in Escape mice. In Stay mice, stimulation of Orx receptors reduces fear conditioning, conflict freezing and startle, and promotes greater attention to the escape hole. This anxiolysis was accompanied by activation of a cluster of inhibitory neurons in the amygdala. A small percentage of those Stay mice also begin escaping; whereas Escape is reversed by the Orx antagonist. Escape mice were also Resilient, and Stay mice Susceptible to stress (SIP), with both conditions reversed by Orx antagonism or stimulation respectively. Together, these results suggest that the Orx receptor may be a useful potential target for anxiolytic or antidepressive therapeutics.

No abstract

Simultaneous analysis of ascorbic acid (AA), uric acid (UA), and dopamine (DA) is desirable as they are important biomarkers that coexist in biological fluids. Electrochemical detection of these molecules can be challenging as their oxidation peaks are poorly resolved at most unmodified electrodes. Modifications are typically necessary for analysis which increase cost and complicate fabrication. Herein, inexpensive and moldable polystyrene thermoplastic electrodes (PS TPEs), that can be used for simultaneous analysis of AA, DA, and UA, without surface modification, were presented. Electrode composition was optimized for conductivity, capacitance, and electrochemistry. Detection limits were 4, 0.9, and 4 μm for AA, DA and UA respectively. PS TPEs were also challenged in urine; excellent recoveries (90-110 %) were seen for AA and UA. DA showed lower recoveries (82 % for 10 μm and 47 % for 5 μm), but in the future, higher recoveries can be achieved through design considerations and further material optimization.